Relapsed Refractory Multiple Myeloma (RRMM)
Conditions
Keywords
B-cell maturation antigen (BCMA), Anti-CD3 monoclonal antibodies (mAbs), G-protein-coupled receptor class C group 5 member D (GPRC5D)
Brief summary
This study is researching a drug called REGN17372 used with another drug called linvoseltamab (each individually called "study drug" or "study drugs" when combined) in participants with relapsed (when a tumor comes back) or refractory (when a tumor does not respond to treatment) multiple myeloma. This study is the first time REGN17372 will be given to humans. The aim of the study is to understand if REGN17372 can be given safely with linvoseltamab, and if so, what dosing regimen should be used for this treatment combination, in comparison with linvoseltamab alone. The study is looking at: * What side effects may happen from taking REGN17372 with linvoseltamab * How well REGN17372 and linvoseltamab, or linvoseltamab alone, work in treating multiple myeloma * What is the best dose of REGN17372 when given with linvoseltamab * How much study drug(s) are in the blood at different times * Whether the body makes antibodies against the study drugs (which could make the study drugs less effective or could lead to side effects) * If and how REGN17372 and linvoseltamab affect the overall quality of life, daily activities, symptoms and treatment side effects based on participant own feedback (Phase 2)
Interventions
DRUGLinvoseltamab
Administered per protocol
DRUGREGN17372+Linvoseltamab
Administered per the protocol
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Phase 1: non-randomized dose escalation Phase 2: randomized dose expansion
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Participants with RRMM who have exhausted (or are not a candidate for) all therapeutic options that are expected to provide meaningful clinical benefit and have received at least 3 lines of therapy as defined in the protocol 2. ECOG performance status score ≤1 3. Participants must have measurable disease for response assessment as described in the protocol 4. Adequate hematologic, cardiac, hepatic, and renal function, as described in the protocol Key
Exclusion criteria
1. Participants with non-secretory MM, active plasma cell leukemia, known amyloidosis, Waldenström macroglobulinemia, or known POEMS syndrome as defined in the protocol 2. Participants who have known MM brain lesions or CNS involvement 3. Participants with a history of PML, a neurocognitive condition or CNS movement disorder, or a history of seizure within 12 months prior to entering screening 4. Prior treatment with GPRC5D-directed immunotherapies (phase 1 and phase 2) and/or prior treatment with a BCMAxCD3 bispecific antibody (phase 2) Note: Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of Dose Limiting Toxicities (DLTs) from the first dose of REGN17372 in combination with linvoseltamab | Up to 35 days | Phase 1 |
| Occurrence of Treatment Emergent Adverse Events (TEAEs) associated with REGN17372 in combination with linvoseltamab | Up to 5 years | Phase 1 |
| Severity of TEAEs associated with REGN17372 in combination with linvoseltamab | Up to 5 years | Phase 1 |
| Very Good Partial Response (VGPR) or better as determined by the investigator using the International Myeloma Working Group (IMWG) response criteria in patients receiving combination study drugs | Within 12 weeks of starting cycle 1 | Phase 2 |
| VGPR or better as determined by the investigator using the IMWG response criteria in patients receiving Linvoseltamab monotherapy | Within 12 weeks of starting cycle 1 | Phase 2 |
| Partial Response (PR) or better as determined by the investigator using the IMWG response criteria in patients receiving combination study drugs | Within 12 weeks of starting cycle 1 | Phase 2 |
| PR or better as determined by the investigator using the IMWG response criteria in patients receiving Linvoseltamab monotherapy | Within 12 weeks of starting cycle 1 | Phase 2 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Concentrations of REGN17372 in serum | Up to 5 years | Phase 1 and Phase 2 |
| Concentrations of linvoseltamab in serum | Up to 5 years | Phase 1 and Phase 2 |
| Occurrence of Anti-Drug Antibodies (ADA) to REGN17372 | Up to 5 years | Phase 1 and Phase 2 |
| Magnitude of ADA to REGN17372 | Up to 5 years | Phase 1 and Phase 2 |
| Incidence of ADA to linvoseltamab | Up to 5 years | Phase 1 and Phase 2 |
| Magnitude of ADA to linvoseltamab | Up to 5 years | Phase 1 and Phase 2 |
| Objective Response Rate (ORR) as assessed by IMWG response criteria as determined by the investigator | Up to 5 years | Phase 1 and Phase 2 |
| Complete response (CR) as assessed by IMWG response criteria as determined by the investigator | Up to 5 years | Phase 1 and Phase 2 |
| VGPR as assessed by IMWG response criteria, as determined by the investigator | Up to 5 years | Phase 1 and Phase 2 |
| Duration of Response (DOR) as assessed by IMWG criteria as determined by the investigator | Up to 5 years | Phase 1 and Phase 2 |
| Progression Free Survival (PFS) as assessed by IMWG criteria as determined by the investigator | Up to 5 years | Phase 1 and Phase 2 |
| Minimal Residual Disease (MRD) negative status (at 10^-5) in participants in CR or better | Up to 5 years | Phase 1 and Phase 2 |
| Overall Survival (OS) | Up to 5 years | Phase 1 and Phase 2 |
| ORR as assessed using the IMWG response criteria as determined by the investigator in patients receiving combination study drugs | Within 12 weeks of starting cycle 1 | Phase 1 |
| VGPR assessed using IMWG criteria as determined by the investigator in patients receiving combination study drugs | Within 12 weeks of starting cycle 1 | Phase 1 |
| Incidence of TEAEs | Up to 5 years | Phase 2 |
| Severity of TEAEs | Up to 5 years | Phase 2 |
| Change from baseline in European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) Global Health Status / Quality of Life (GHS/QoL) | Up to 5 years | Phase 2 The EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including global health status/quality of life, functional Scales (physical, role, emotional, cognitive, and social), symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Participants rate items on a 4-point scale, with 1 as "not at all" and 4 as "very much" |
| Change from baseline in EORTC QLQ-C30 Physical Functioning (PF) | Up to 5 years | Phase 2 |
| Change from baseline in EORTC QLQ-C30 Role Functioning (RF) | Up to 5 years | Phase 2 |
| Change from baseline in EORTC QLQ-C30 pain | Up to 5 years | Phase 2 |
| Change from baseline in EORTC QLQ-C30 fatigue | Up to 5 years | Phase 2 |
| Time to definitive deterioration in EORTC QLQ-C30 GHS/QoL | Up to 5 years | Phase 2 |
| Time to definitive deterioration in EORTC QLQ-C30 PF | Up to 5 years | Phase 2 |
| Time to definitive deterioration in EORTC QLQ-C30 RF | Up to 5 years | Phase 2 |
| Time to definitive deterioration in EORTC QLQ-C30 pain | Up to 5 years | Phase 2 |
| Time to definitive deterioration in EORTC QLQ-C30 fatigue | Up to 5 years | Phase 2 |
| Time to first improvement in EORTC QLQ-C30 GHS/QoL | Up to 5 years | Phase2 |
| Time to first improvement in EORTC QLQ-C30 PF | Up to 5 years | Phase 2 |
| Time to first improvement in EORTC QLQ-C30 RF | Up to 5 years | Phase 2 |
| Time to first improvement in EORTC QLQ-C30 pain | Up to 5 years | Phase 2 |
| Time to first improvement in EORTC QLQ-C30 fatigue | Up to 5 years | Phase 2 |
| Change from baseline in EORTC QLQ-Multiple Myeloma Module (MY20) Disease Symptoms (DS) | Up to 5 years | Phase 2 The EORTC QLQ-MY20 is a self -administered instrument to assess QoL in persons with MM. This 20-item questionnaire measures the following domains: symptom scales, including disease symptoms (6 items) and symptoms related to side effects of treatment (10 items); function scale and future perspective (3 items); and body image (1 item). A high score represents a high level of symptoms or problems |
| Time to definitive deterioration in EORTC QLQ-MY20 DS | Up to 5 years | Phase 2 |
| Time to first improvement in EORTC QLQ-MY20 DS | Up to 5 years | Phase 2 |
| Change from baseline in EORTC QLQ-MY20 Treatment Side Effects (TSE) | Up to 5 years | Phase 2 |
| Time to definitive deterioration in EORTC QLQ-MY20 TSE | Up to 5 years | Phase 2 |
| Time to first improvement in EORTC QLQ-MY20 TSE | Up to 5 years | Phase 2 |
| Change from baseline in EuroQoL-5 Dimensions, 5-level Questionnaire (EQ-5D-5L) Visual Analogue Score (VAS) (EQ-5D-5L VAS) | Up to 5 years | Phase 2 The EQ-5D-5L consists of EQ-5D descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems |
| Time to definitive deterioration in EQ-5D-5L VAS | Up to 5 years | Phase 2 |
| Time to first improvement in EQ-5D-5L VAS | Up to 5 years | Phase 2 |
| Patient-reported overall impact of treatment toxicity measured by Functional Assessment of Cancer Therapy (FACIT) Item GP5 | Up to 5 years | Phase 2 The FACIT Item GP5 will be used to assess the patient-reported impact of treatment toxicity that uses a single item "I am bothered by side effects of treatment" on a 5-point scale (0 = not at all, 1 = a little bit, 2 = somewhat, 3 = quite a bit, 4 = very much) |
| Patient-reported tolerability as measured by the Patient Reported Outcome-Common Terminology Criteria for Adverse Events (PRO-CTCAE) | Up to 5 years | Phase 2 The PRO-CTAE questionnaire assesses side effects and symptoms in cancer clinical trials using a PRO-CTCAE score. The PRO-CTCAE includes an item library of 124 items representing 78 symptomatic AEs drawn from the CTCAE |
Countries
Australia, Greece
Contacts
CONTACTClinical Trials Administrator
STUDY_DIRECTORClinical Trial Management
Regeneron Pharmaceuticals
Outcome results
None listed